1. Field of the Invention
This invention relates to a pharmaceutical composition of Levocarnitine (L-carnitine) or its derivatives, and its use for treating hyperuricemia and any a related disorder.
2. Description of the Background
Hyperuricemia (male: serum uric acid (SUA)≧420 mmol/L, female: SUA≧360 mmol/L) and gout is caused by purine metabolic disorder, The activity of the purine metabolic enzyme either congenital or acquired defect, which cause the uric acid either excess, insufficient or either way, cause the uric acid of blood plasma out of the saturation; The SUA slat educed and crystallized in joints, connective tissue and kidney result in the gout episode. The natural progression and clinical manifestations of gout is includes: 1. none symptoms hyperuricemia state; 2. acute onset of gouty arthritis; 3. intermission of gout 4. chronic arthritis of gouty tophus.
The primary hyperuricemia is fewer clinically, recently due to improvement of nutritional status, lengthening of average life expectancy, and people's attention of this disease etc reason, the incidence has been increasing gradually. Prevalence has been increasing with age, particularly in males, fewer in females, which occur more after menopause. Cases reports abroad have shown it related with family history, most of them autosomal recessive inheritances. It happens more in brainworkers and who has favorable economic status; analysis of risk factor indicated that the hyperuricemia in females, have correlation with age, body mass index (BMI), blood inosine, erythrocyte sedimentation rate, while has no correlation with cholesterol and triglyceride (TG); The SUA levels of males have significant correlation with BMI and blood inosine. Epidemiological reports in Spain indicated the rate of hyperuricemia patients with cardiovascular disease and other risk factors are increasing related with age. Multiple regression analysis results suggested that glucose, adiposity and hyperuricemia, ware significantly related to each other; And also related to hypercholesterolemia, hypertension and smoking.
Either primary or secondary hyperuricemia, except a few caused by drugs, most of them lack the treating with pathogeny, so there is not a radical cure. There are four intentions for clinical treatment: 1. to terminate the acute arthritis episode; 2. to prevent arthritis recrudesce; 3. to correct the hyperuricemia, prevent and cure urate deposits in kidneys, joints and so on to cause the complications 4. to prevent and cure urate nephrolithiasis formation.
The treating of gouty arthritis includes: 1) Acute paroxysm stage: colchicines, non-steroidal anti-inflammatory drugs, adrenocorticotropic hormone (ACTH) and prednisone; 2) drugs for reduce serum uric acid: included two kinds of drugs as uricosuric agents and uric acid synthesis inhibitions.
The commonly used uricosuric agents (via inhibition of renal tubular reabsorption of uric acid) are: (1) Probenecid; (2) Sulfinpyrazone; (3) Benzbromarone. During administration of uricosuric agents, orally taking sodium bicarbonate 3-6 g/day to alkalify the urine, liquid retention amount needs keeping on more than 2000 ml a day for advantages in excreted of uric acid.
Uric acid syntheses inhibition agents: at present only allopurinol is available (can inhibit the xanthine oxidase, result in the hypoxanthine and xanthine can't be transformed to uric acid).
It was found that those two kinds of drugs without function of anti-inflammatory and analgesic, and during medication they may mobilize the uric acid into the blood circulation, and induce the acute arthritis attack, so they are not recommended to use at acute paroxysm stage. Selection of agents for treating gout often based on renal function and the quantity of 24 hours uric acid excreted in clinic. If the quantity is below 4.8 mmol/day (800 mg/day), chose uricosuric; if the renal function is declined and the quantity of uric acid excreted above 4.8 mmol/day, chose the drugs for uric acid syntheses inhibitor; if the patient has significantly increased quantity of uric acid excreted and gouty tophus formation, combined the both therapies mentioned above are recommended.
However, all therapies mentioned above aren't etiological treatment. The anti-hyperuricemia agents all have different side effect or toxicity, for example, the drugs for excrete uric acid can cause the crystallization of urate deposition in the urethra, lead to the renal dysfunction and renal colic; uricase inhibitor, allopurinol also myelosuppression, hepatic lesion, dermological toxicity and side effect etc. Therefore, it is necessary to find an effective and relative safer medical composition for treatment of hyperuricemia and related disease.